Irinotecan Hydrochloride and Cetuximab with or without Ramucirumab in Treating Patients with Advanced Colorectal Cancer with Progressive Disease after Treatment with Bevacizumab-Containing Chemotherapy

Basic Trial Information

Phase

Type

Status

Age

Trial IDs

Phase II

Treatment

Active

18 and over

E7208NCI-2011-02018, CDR0000666736, ECOG-E7208, NCT01079780

Trial Description

Summary

This randomized phase II trial studies the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with colorectal cancer that has spread to other places in the body and is progressive (spreading or getting worse) after treatment with bevacizumab-containing chemotherapy. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, may interfere with the ability of tumor cells to grow and spread. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) for the addition of the anti-angiogenic antibody, ramucirumab, in combination with irinotecan (irinotecan hydrochloride) and cetuximab as second line therapy for patients with Kirsten rat sarcoma viral oncogene homolog (K-ras) wild-type colorectal cancer, as compared to the patients without the antibody.

II. To evaluate the response rate for irinotecan, cetuximab and ramucirumab in this patient population.

III. To evaluate the grade 3-4 toxicity rates for the combination in this patient population.

IV. To evaluate the overall survival for irinotecan, cetuximab, and ramucirumab in this patient population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients were randomized to arms I or II until 12/17/2013. After the closing of arm II, patients are randomized to arms I or III.

In all arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 1 year and then every 6 months for 3 years.

Eligibility Criteria

Inclusion Criteria:

Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy

Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or agree to abstain from sexual intercourse during their participation in the study and for 3 months following completion of their participation

Patients must have measurable disease

Histologically documented adenocarcinoma (including the histologic variants of adenocarcinoma) of the colon or rectum

Patients K-ras status must be wild type (not mutated); K-ras status determination may be based on either primary or metastatic tumor

NOTE: the assay must be performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory

Patients must have had prior first-line therapy with oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer

International normalized ratio (INR) =< 1.6 (unless receiving anticoagulation therapy); patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin; if receiving warfarin, the patient must have an INR =< 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy)

No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for this disease; chemotherapy drugs and bevacizumab may be stopped and started as long as no prior disease progression requiring change in chemotherapy agents occurred

No other cancer requiring therapy within the last 3 years (except in situ carcinoma or nonmelanoma skin cancer)

Patients must not have an acute or subacute intestinal obstruction; no history of bowel obstruction, gastrointestinal (GI) perforation, major abdominal surgery with bowel resection, or perirectal/perianal abscess within 6 months prior to randomization

Patient must not have a history of inflammatory bowel disease requiring pharmacological and/or surgical intervention within the 12 months prior to randomization

Patient must not have a known allergy to any of the treatment components

Sheridan

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